Volume 27, Issue 2 And 3 (3-2023)                   IBJ 2023, 27(2 And 3): 117-125 | Back to browse issues page

PMID: 37070674
PMCID: PMC10314763

XML Print


Background: Infection is one of the significant challenges in medical implant-related surgeries. Despite systemic antibiotic therapies, bacterial growth after implantation may cause implant failure. Nowadays, unlike the systemic therapy, local controlled release of antibiotic agents is considered an effective approach for the prevention of implant-related infections. The present study aimed to develop a niosomal nanocarrier incorporated into fibroin films for local and continuous delivery of thymol, a natural plant-derived antimicrobial agent for preventing infections caused by implant-related.
Methods: Niosomes containing thymol were prepared by thin-film hydration technique. Thymol sustained release from the prepared films was assessed for 14 days. Antibacterial activities of the synthesized films were also evaluated by the agar diffusion technique against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus.
Results: The release behavior from the niosomal thymol films showed a sustained manner, in which the amount of the released thymol reached 40% after 14 days. The films containing thymol with and without niosome showed a significant viability against L929 fibroblast cells compared to other groups after 24 and 48 h, using MTT assay. Also, samples exhibited potent antibacterial activity against Gram-negative and Gram-positive bacteria.
Conclusion: The results of this study demonstrate that the niosomal thymol-loaded fibroin film is a promising candidate for the controlled release of thymol and prevention of implant-related infection.

1. Zimmerli W. Infection and musculoskeletal conditions: prosthetic-joint-associated infections. Best practice and research. clinical rheumatology 2006; 20(6): 1045-1063. [DOI:10.1016/j.berh.2006.08.003]
2. Nowakowska J, Landmann R, Khanna N. Foreign body infection models to study host-pathogen response and antimicrobial tolerance of bacterial biofilm. Antibiotics 2014; 3(3): 378-397. [DOI:10.3390/antibiotics3030378]
3. Song Z, Borgwardt L, Hoiby N, Wu H, Sorensen TS, Borgwardt A. Prosthesis infections after orthopedic joint replacement: the possible role of bacterial biofilms. Orthopedic reviews 2013; 5(2): 65-71. [DOI:10.4081/or.2013.e14]
4. Visscher LE, Dang HP, Knackstedt MA, Hutmacher DW, Tran PA. 3D printed Polycaprolactone scaffolds with dual macro-microporosity for applications in local delivery of antibiotics. Materials science and engineering: C 2018; 87: 78-89. [DOI:10.1016/j.msec.2018.02.008]
5. Bakkali F, Averbeck S, Averbeck D, Idaomar M. Biological effects of essential oils-a review. Food and chemical toxicology 2008; 46(2): 446-475. [DOI:10.1016/j.fct.2007.09.106]
6. Benchaar C, Calsamiglia S, Chaves AV, Fraser G, Colombatto D, McAllister TA, Beauchemin KA. A review of plant-derived essential oils in ruminant nutrition and production. Animal feed science and technology 2008; 145(1-4): 209-228. [DOI:10.1016/j.anifeedsci.2007.04.014]
7. Evans JD, Martin SA. Effects of thymol on ruminal microorganisms. Current microbiology 2000; 41(5): 336-340. [DOI:10.1007/s002840010145]
8. Marchese A, Orhan IE, Daglia M, Barbieri R, Di Lorenzo A, Nabavi SF, Gortzi O, Izadi M, Nabavi SM. Antibacterial and antifungal activities of thymol: A brief review of the literature. Food chemistry 2016; 210: 402-414. [DOI:10.1016/j.foodchem.2016.04.111]
9. Wattanasatcha A, Rengpipat S, Wanichwecharungruang S. Thymol nanospheres as an effective anti-bacterial agent. International journal of pharmaceutics 2012; 434(1-2): 360-365. [DOI:10.1016/j.ijpharm.2012.06.017]
10. Zhang Y, Zhang Y, Zhu Z, Jiao X, Shang Y, Wen Y. Encapsulation of thymol in biodegradable nanofiber via coaxial eletrospinning and applications in fruit preservation. Journal of agricultural and food chemistry 2019; 67(6): 1736-1741. [DOI:10.1021/acs.jafc.8b06362]
11. Rodríguez López MI, Mercader Ros MT, López Miranda S, Pellicer JA, Pérez Garrido A, Pérez Sánchez H, Núñez Delicado E, Gabaldón JA. Thorough characterization and stability of HP-β-cyclodextrin thymol inclusion complexes prepared by microwave technology: A required approach to a successful application in food industry. Journal of the science of food and agriculture 2019; 99(3): 1322-1333. [DOI:10.1002/jsfa.9307]
12. Engel JB, Heckler C, Tondo EC, Daroit DJ, da Silva Malheiros P. Antimicrobial activity of free and liposome-encapsulated thymol and carvacrol against Salmonella and Staphylococcus aureus adhered to stainless steel. International journal of food microbiology 2017; 252: 18-23. [DOI:10.1016/j.ijfoodmicro.2017.04.003]
13. Sheorain J, Mehra M, Thakur R, Grewal S, Kumari S. In vitro anti-inflammatory and antioxidant potential of thymol loaded bipolymeric (tragacanth gum/chitosan) nanocarrier. International journal of biological macromolecules 2019; 125: 1069-1074. [DOI:10.1016/j.ijbiomac.2018.12.095]
14. Asprea M, Leto I, Bergonzi MC, Bilia AR. Thyme essential oil loaded in nanocochleates: Encapsulation efficiency, in vitro release study and antioxidant activity. LWT 2017; 77: 497-502. [DOI:10.1016/j.lwt.2016.12.006]
15. Pan K, Chen H, Davidson PM, Zhong Q. Thymol nanoencapsulated by sodium caseinate: physical and antilisterial properties. Journal of agricultural and food chemistry 2014; 62(7): 1649-1657. [DOI:10.1021/jf4055402]
16. Amusa AS, Satish J, Gopalakrishna P. In vitro activities of fluoroquinolones entrapped in non-ionic surfactant vesicles against ciprofloxacin-resistant bacteria strains. journal of pharmaceutical technology and drug research 2012; 1(1): 5. [DOI:10.7243/2050-120X-1-5]
17. Akbari V, Sadeghi H, Abedi D, Pardakhty A, Shafizadegan S. Antimicrobial properties of non-ionic surafactant vesicles containing ciprofloxacin. Research in pharmaceutical sciences 2012; 7(5): 15. [DOI:10.1007/s11051-013-1556-y]
18. Kopermsub P, Mayen V, Warin C. Potential use of niosomes for encapsulation of nisin and EDTA and their antibacterial activity enhancement. Food research international 2011; 44(2): 605-612. [DOI:10.1016/j.foodres.2010.12.011]
19. Barakat HS, Kassem MA, El Khordagui LK, Khalafallah NM. Vancomycin-eluting niosomes: A new approach to the inhibition of staphylococcal biofilm on abiotic surfaces. AAPS pharmSciTech 2014; 15(5): 1263-1274. [DOI:10.1208/s12249-014-0141-8]
20. NVS M, Saini A. Niosomes: a novel drug delivery system. International journal of research in pharmacy and chemistry 2011; 1(3): 498-511.
21. Mahdiun F, Mansouri S, Khazaeli P, Mirzaei R. The effect of tobramycin incorporated with bismuth-ethanedithiol loaded on niosomes on the quorum sensing and biofilm formation of Pseudomonas aeruginosa. Microbial pathogenesis 2017; 107: 129-135. [DOI:10.1016/j.micpath.2017.03.014]
22. Akhtar N, Kumar Singh R, Pathak K. Exploring the potential of complex-vesicle based niosomal ocular system loaded with azithromycin: Development of in situ gel and ex vivo characterization. Pharmaceutical and biomedical research 2017. 3(1): 22-33. [DOI:10.18869/acadpub.pbr.3.1.22]
23. Rinaldi F, del Favero E, Moeller J, Hanieh PN, Passeri D, Rossi M, Angeloni L, Venditti I, Marianecci C, Carafa M. Hydrophilic silver nanoparticles loaded into niosomes: Physical-chemical characterization in view of biological applications. Nanomaterials 2019; 9(8): 1177. [DOI:10.3390/nano9081177]
24. Srivastava CM, Purwar R, Kannaujia R, Sharma D. Flexible silk fibroin films for wound dressing. Fibers and polymers 2015; 16(5): 1020-1030. [DOI:10.1007/s12221-015-1020-y]
25. Karageorgiou V, Meinel L, Hofmann S, Malhotra A, Volloch V, Kaplan D. Bone morphogenetic protein-2 decorated silk fibroin films induce osteogenic differentiation of human bone marrow stromal cells. Journal of biomedical materials research. Part A 2004; 71(3): 528-537. [DOI:10.1002/jbm.a.30186]
26. Bhardwaj N, Kundu SC. Silk fibroin protein and chitosan polyelectrolyte complex porous scaffolds for tissue engineering applications. Carbohydrate polymers 2011; 85(2): 325-333. [DOI:10.1016/j.carbpol.2011.02.027]
27. Wenk E, Merkle HP, Meinel L. Silk fibroin as a vehicle for drug delivery applications. Journal of controlled release 2011; 150(2): 128-141. [DOI:10.1016/j.jconrel.2010.11.007]
28. Najafloo R, Baheiraei N, Imani R. Synthesis and characterization of collagen/calcium phosphate scaffolds incorporating antibacterial agent for bone tissue engineering application. Iranian biomedical journal 2020; 27(2-3): 1-9. [DOI:10.1177/0883911520966692]
29. Lutwyche P, Cordeiro C, Wiseman DJ, St Louis M, Uh M, Hope MJ, Webb MS, Finlay BB. Intracellular delivery and antibacterial activity of gentamicin encapsulated in pH-sensitive liposomes. Antimicrobial agents and chemotherapy 1998; 42(10): 2511-2520. [DOI:10.1128/AAC.42.10.2511]
30. Najafloo R, Behyari M, Imani R, Nour S. A mini-review of Thymol incorporated materials: Applications in antibacterial wound dressing. Journal of drug delivery science and technology 2020; 60:101904. [DOI:10.1016/j.jddst.2020.101904]
31. Alemi A, Reza JZ, Haghiralsadat F, Jaliani HZ, Karamallah MH, Hosseini SA, Karamallah SH. Paclitaxel and curcumin coadministration in novel cationic PEGylated niosomal formulations exhibit enhanced synergistic antitumor efficacy. Journal of nanobiotechnology 2018, 16(1): 28. [DOI:10.1186/s12951-018-0351-4]
32. Rungphanichkul N, Nimmannit U, Muangsiri W, Rojsitthisak P. Preparation of curcuminoid niosomes for enhancement of skin permeation. Die Pharmazie; 66(8): 570-575.
33. Behyari M, Imani R, Keshvari H. Evaluation of silk fibroin nanofibrous dressing incorporating niosomal propolis, for potential use in wound healing. Fibers and polymers 2021; 1-12. [DOI:10.1007/s12221-021-0973-2]
34. Tavano L, Picci N, Ioele G, Muzzalupo R. Tetracycline-niosomes versus Tetracycline Hydrochlo-ride-niosomes: how to modulate encapsulation and percutaneous permeation properties. Journal of drug 2017; 1(2): 1-6. [DOI:10.24218/jod.2017.6]
35. Sohrabi S, Haeri A, Mahboubi A, Mortazavi A, Dadashzadeh S. Chitosan gel-embedded moxifloxacin niosomes: an efficient antimicrobial hybrid system for burn infection. International journal of biological macromolecules 2016; 85: 625-633. [DOI:10.1016/j.ijbiomac.2016.01.013]
36. Bayindir ZS, Yuksel N. Characterization of niosomes prepared with various nonionic surfactants for paclitaxel oral delivery. Journal of pharmaceutical sciences 2010; 99(4): 2049-2060. [DOI:10.1002/jps.21944]
37. Jin Y, Wen J, Garg S, Liu D, Zhou Y, Teng L, Zhang W. Development of a novel niosomal system for oral delivery of Ginkgo biloba extract. International journal of nanomedicine 2013; 8: 421. [DOI:10.2147/IJN.S37984]
38. Jiji S, Udhayakumar S, Rose C, Muralidharan C, Kadirvelu K. Thymol enriched bacterial cellulose hydrogel as effective material for third degree burn wound repair. International journal of biological macromolecules 2019; 122: 452-460. [DOI:10.1016/j.ijbiomac.2018.10.192]
39. Gabbai Armelin PR, Sales LS, Ferrisse TM, De Oliveira AB, De Oliveira JR, Giro EMA, Brighenti FL. A systematic review and meta-analysis of the effect of thymol as an anti-inflammatory and wound healing agent: A review of thymol effect on inflammation and wound healing. Phytotherapy research 2022; 36(9): 3415-3443. [DOI:10.1002/ptr.7541]
40. Najafloo R, Behyari M, Imani R, Nour S. A mini-review of thymol incorporated materials: Applications in antibacterial wound dressing. Journal of drug delivery science and technology 2020; 60 :101904. [DOI:10.1016/j.jddst.2020.101904]
41. Costa MF, Durço AO, Rabelo TK, Barreto RdSS, Guimarães AG. Effects of carvacrol, thymol and essential oils containing such monoterpenes on wound healing: A systematic review. Journal of pharmacy and pharmacology 2019; 71(2): 141-155. [DOI:10.1111/jphp.13054]
42. Trombetta D, Castelli F, Sarpietro MG, Venuti V, Cristani M, Daniele C, Saija A, Mazzanti G, Bisignano G. Mechanisms of antibacterial action of three monoterpenes. Antimicrobial agents and chemotherapy 2005; 49(6): 2474-2478. [DOI:10.1128/AAC.49.6.2474-2478.2005]
43. Hancock RE. The bacterial outer membrane as a drug barrier. Trends in microbiology 1997; 5(1): 37-42. [DOI:10.1016/S0966-842X(97)81773-8]
44. Helander IM, Alakomi H-L, Latva Kala K, Mattila-Sandholm T, Pol I, Smid EJ, Gorris LG, von Wright A: Characterization of the action of selected essential oil components on Gram-negative bacteria. Journal of agricultural and food chemistry 1998; 46(9): 3590-3595. [DOI:10.1021/jf980154m]
45. Oliveira W, Silva P, Silva R, Silva G, Machado G, Coelho L, Correia M. Staphylococcus aureus and Staphylococcus epidermidis infections on implants. Journal of hospital infection 2018; 98(2): 111-117. [DOI:10.1016/j.jhin.2017.11.008]

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.